Alexandros Marinos 🏴‍☠️ on X: "It's also odd that the fluvoxamine arm started earlier, (since the ivm arm had to be restarted) but they both reached the ideal number of patients at the same time. It is particularly galling given the following statement by the trial lead in an email: https://t.co/rVrcYUs9KY" / X

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Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 3, 2022
Why was the TOGETHER trial ivm arm terminated? NEJM Paper says the futility thresholds were 20/40/60% posterior probability of efficacy. Website says that the trial was stopped for futility. Yet the published probabilities of efficacy are all >60%. What am I missing?
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
Indeed, from an interview of the principal investigator, we have him saying clearly that that they intended to get 800 patients, and they stopped about 85% of the way. Given that the Gamma variant was lifting, this could have made a huge difference. halifaxexaminer.ca/featured/whats…
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
To demonstrate why this matters, the results released on August 11, 2021, calculated a probability of superiority at 76%. The results we saw published report it at 79.4%. This could mean nothing, but it might indicate that the last few patients admitted fared exceedingly well.
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
Why would those patients fare better than the ones before them? It may be an artifact of chance. Or it might be that the Gamma variant had just started to recede. covariants.org/per-variant?co…
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
This may be a good opportunity to remind everyone that the Gamma variant was the deadliest of the major VOCs, significantly moreso than Delta, being the one that vaccines also had the biggest difficulty protecting against. thelancet.com/journals/lance…
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
Also worth mentioning that 85% of recruitment target wasn't even a predefined interim analysis point. And of course, if the investigators are allowed to analyze the data at any point they please and stop the study based on those results, they can produce any result.
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
In fact, the fluvoxamine trial, which ran mostly in parallel, also had several interim analyses planned, but the threshold was fixed at 40%. Why the double standard with IVM?
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
Some folks are pointing that the published protocol indeed mentions 681 as the planned number of patients. However the initial (25-Mar-2021) protocol on the together trial website says this, confirming Mills' interview. static1.squarespace.com/static/6112a25…
Alexandros Marinos 🏴‍☠️
@alexandrosM
Apr 4, 2022
It is only in version 3 of the protocol, dated 22-June-2022 that 681 participants per arm are contemplated for *all arms* of the trial. And yet, Fluvoxamine somehow extended to 741+756 patients for its analysis. static1.squarespace.com/static/6112a25…
Alexandros Marinos 🏴‍☠️
@alexandrosM
It's also odd that the fluvoxamine arm started earlier, (since the ivm arm had to be restarted) but they both reached the ideal number of patients at the same time. It is particularly galling given the following statement by the trial lead in an email: stevekirsch.substack.com/p/did-the-toge…
10:40 PM · Apr 4, 2022